We are seeking quantitative associations among the following processes as a means for developing information both on the mechanisms of chemical carcinogenesis and as a pre-screen for environmental carcinogens: oncogenic transformation, cytotoxicity, chemical mutagenesis, DNA synthesis, and the production and repair of alkali-labile lesions in the DNA. This is done with cultured fibroblast (Chinese hamster V79 and mouse embryo C3H/10T1/2 cells) treated with various doses of four simple alkylating agents. We are also attempting to develop an in vivo-in vitro system for determining oncogenic transformation by chemicals that require metabolic activation. This involves administration of liver carcinogens to partially hepactectomized rats, culturing of the hepatocytes, and observing for oncogenic transformation.